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MD4291C1 - Medicinal preparation for the treatment of otitis - Google Patents

Medicinal preparation for the treatment of otitis Download PDF

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Publication number
MD4291C1
MD4291C1 MDA20130100A MD20130100A MD4291C1 MD 4291 C1 MD4291 C1 MD 4291C1 MD A20130100 A MDA20130100 A MD A20130100A MD 20130100 A MD20130100 A MD 20130100A MD 4291 C1 MD4291 C1 MD 4291C1
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MD
Moldova
Prior art keywords
otitis
treatment
preparation
medicinal preparation
medicinal
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MDA20130100A
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Romanian (ro)
Russian (ru)
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MD4291B1 (en
Inventor
Михаил МАНЮК
Владимир ВАЛИКА
Серджиу ПАРИЙ
Ливия УНКУ
Полина АБАБИЙ
Еуджениу НИКОЛАЙ
Роман ШТЕФЫРЦЭ
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Государственный Медицинский И Фармацевтический Университет "Nicolae Testemitanu" Республики Молдова
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Priority to MDA20130100A priority Critical patent/MD4291C1/en
Publication of MD4291B1 publication Critical patent/MD4291B1/en
Publication of MD4291C1 publication Critical patent/MD4291C1/en

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Abstract

The invention relates to medicine, in particular to otorhinolaryngology, namely to a medicinal preparation for the treatment of otitis.According to the invention, the claimed medicinal preparation contains for 50 ml:

Description

Invenţia se referă la medicină, în special la otorinolaringologie, şi anume la un preparat medicamentos pentru tratamentul otitelor. The invention relates to medicine, especially to otorhinolaryngology, namely to a medicinal preparation for the treatment of otitis.

Este cunoscută utilizarea preparatului medicamentos combinat Otinum sub formă de soluţie 10 ml, în calitate de medicament cu aplicare topică în tratamentul afecţiunilor urechii [1]. It is known to use the combined medicinal preparation Otinum in the form of a 10 ml solution, as a medicine with topical application in the treatment of ear diseases [1].

Dezavantajul preparatului menţionat constă în faptul că nu posedă efect regenerativ şi nu poate fi utilizat la otitele medii cu perforarea timpanului. The disadvantage of the mentioned preparation is that it does not have a regenerative effect and cannot be used for otitis media with perforation of the tympanic membrane.

Preparatele medicamentoase combinate presupun asocierea într-un singur preparat a doi sau mai mulţi agenţi cu acţiune terapeutică diferită asupra mai multor mecanisme ce intervin la declanşarea stării patologice. Medicamentele combinate manifestă sporirea efectului terapeutic prin acţiune sinergică, reducerea efectelor secundare la utilizarea unor doze mai mici de substanţe active cu reacţii adverse diferite, creşterea tolerabilităţii medicaţiei şi complianţa tratamentului. Combined medicinal preparations involve the association in a single preparation of two or more agents with different therapeutic action on several mechanisms involved in triggering the pathological condition. The combined drugs show the increase of the therapeutic effect through synergistic action, the reduction of side effects when using lower doses of active substances with different side effects, the increase of the tolerability of the medication and the compliance of the treatment.

Problema pe care o rezolvă invenţia solicitată constă în extinderea gamei de preparate medicamentoase sub formă de picături auriculare pentru tratamentul otitelor externe, otitelor medii acute şi otitelor medii cronice atât la cele fără perforaţia membranei timpanice, cât şi la cele perforative. The problem that the requested invention solves consists in expanding the range of medicinal preparations in the form of ear drops for the treatment of otitis externa, acute otitis media and chronic otitis media both in those without perforation of the tympanic membrane and in those with perforation.

Conform invenţiei, preparatul medicamentos revendicat conţine pentru 50 ml: According to the invention, the claimed medicinal preparation contains for 50 ml:

ciprofloxacină clorhidrat, g 0,148…0,152 ulei volatil de busuioc, g 0,198…0,202 loratadin, g 0,009…0,015 dexametazon, g 0,009…0,015 polisorbat 20, g 1,990…2,010 polietilenglicol 400, g 4,990…5,010 nipagin, g 0,019…0,020 soluţie tampon de citrat cu pH 7,8, g 0,010…0,020 apă distilată restul. ciprofloxacin hydrochloride, g 0.148...0.152 volatile oil of basil, g 0.198...0.202 loratadine, g 0.009...0.015 dexamethasone, g 0.009...0.015 polysorbate 20, g 1.990...2.010 polyethylene glycol 400, g 4.990...5.010 nipagin, g 0.019 ...0.020 buffer solution of citrate with pH 7.8, g 0.010...0.020 distilled water the rest.

Rezultatul constă în obţinerea unui preparat medicamentos combinat mai efectiv, rezultativ şi mai ieftin. The result consists in obtaining a more effective, effective and cheaper combined medicinal preparation.

Avantajul constă în aceea că preparatul propus datorită combinaţiei ingredientelor active posedă acţiune sinergică manifestată prin efectele regenerativ mai evidenţiat, precum şi antimicrobian, antiinflamator şi antiexsudativ, fapt ce contribuie la majorarea eficacităţii tratamentului otitelor nesupurative şi supurative. The advantage lies in the fact that the proposed preparation, thanks to the combination of active ingredients, has a synergistic action manifested by more pronounced regenerative effects, as well as antimicrobial, anti-inflammatory and anti-exudative, which contributes to increasing the effectiveness of the treatment of non-suppurative and suppurative otitis.

Ciprofloxacina reprezintă un remediu antibacterian din grupa fluorchinolonilor cu spectru larg de acţiune, activ faţă de un număr impunător de germeni patogeni. Mecanismul de acţiune constă în blocarea ADN-girazei microorganismelor sensibile şi a replicării ADN-ului. Fluorul este responsabil de lărgirea spectrului antibacterian pentru bacteriile gram-negative şi extinderea spectrului la bacteriile gram-pozitive. Ciclul piperazinic face preparatul activ contra pseudomonadelor. Ciprofloxacin is an antibacterial remedy from the group of fluoroquinolones with a broad spectrum of action, active against an impressive number of pathogenic germs. The mechanism of action consists in blocking DNA gyrase of sensitive microorganisms and DNA replication. Fluoride is responsible for broadening the antibacterial spectrum for gram-negative bacteria and extending the spectrum for gram-positive bacteria. The piperazine cycle makes the preparation active against pseudomonads.

Busuiocul (Ocimum basilicum) este o plantă cu mai multe efecte terapeutice. Posedă actiune antimicrobiană, antiinflamatorie, regenerativă, calmantă, uşor anestezică etc. Este pe larg utilizat inclusiv în tratamentul afecţiunilor tractului respirator superior şi inferior. Basil (Ocimum basilicum) is a plant with several therapeutic effects. It has antimicrobial, anti-inflammatory, regenerative, calming, slightly anesthetic action, etc. It is widely used including in the treatment of upper and lower respiratory tract diseases.

Loratadinul este un antiseptic cu acţiune periferică de lungă durată, derivat al piperidinei care blocheaza H1-receptorii histaminergici periferici. Nu depăşeste bariera hematoencefalică, are acţiune antialergică, antiexsudativă şi antipruriginoasă. Totodată scade permeabilitatea capilarelor, inlatură spasmul musculaturii netede, previne edemele ţesuturilor. Loratadine is an antiseptic with long-term peripheral action, a derivative of piperidine that blocks peripheral histaminergic H1-receptors. It does not cross the blood-brain barrier, has anti-allergic, anti-exudative and anti-pruritic action. At the same time, it decreases capillary permeability, removes smooth muscle spasm, prevents tissue edema.

Dexametazonul este un antiinflamator steroidian, glucocorticosteroid puternic lipsit de proprietăţi mineralocorticoide (nu reţine sodiul în organism). În aplicaţia topică posedă actiune antiinflamatoare, antipruriginoasă şi vasoconstrictoare. Dexamethasone is a steroid anti-inflammatory, strong glucocorticosteroid without mineralocorticoid properties (does not retain sodium in the body). In topical application, it has anti-inflammatory, antipruritic and vasoconstrictive action.

Forma farmaceutică reprezintă o emulsie uleioasă de tip ulei/apă pentru uz extern cu continut de ciprofloxacină clorhidrat, loratadin, dexametazon şi ulei volatil de busuioc. Preparatul medicamentos policomponent posedă un spectru de acţiune multidirecţionat şi asigură un efect terapeutic complex. Preparatul este caracterizat prin componenţa cantitativă şi calitativă valoroasă, conţinutul unor principii bioactive, lipsa elementelor nocive, simplitatea proceselor tehnologice. The pharmaceutical form is an oily emulsion of oil/water type for external use containing ciprofloxacin hydrochloride, loratadine, dexamethasone and volatile basil oil. The polycomponent medicinal preparation has a multidirectional spectrum of action and ensures a complex therapeutic effect. The preparation is characterized by its valuable quantitative and qualitative composition, the content of bioactive principles, the absence of harmful elements, the simplicity of the technological processes.

Etapele de elaborare a preparatului medicamentos The stages of the development of the medicinal preparation

1. Studiul compatibilităţii ciprofloxacinei şi uleiului de busuioc în aceeaşi formă farmaceutică. 1. Compatibility study of ciprofloxacin and basil oil in the same pharmaceutical form.

2. Elaborarea compoziţiei şi a tehnologiei de preparare a picăturilor auriculare. 2. Elaboration of the composition and preparation technology of ear drops.

2.1. Preformularea şi elaborarea tehnologiei de preparare optime a picăturilor auriculare cu conţinut de ciprofloxacină şi ulei volatil de busuioc. 2.1. Preformulation and development of the optimal preparation technology of auricular drops containing ciprofloxacin and volatile basil oil.

3. Elaborarea metodelor de analiză a picăturilor auriculare cu conţinut de ciprofloxacină şi ulei de busuioc. 3. Development of methods for analyzing ear drops containing ciprofloxacin and basil oil.

4. Standardizarea formei farmaceutice. 4. Standardization of the pharmaceutical form.

Procesul tehnologic de preparare a unguentului The technological process of preparing the ointment

Pregătirea emulsiei primare. Într-o cească de porţelan se introduce polisorbat 20, la care se adaugă cu picatura ulei de busuioc, se amestecă bine până la emulsionarea uleiului. Preparation of primary emulsion. Polysorbate 20 is introduced into a porcelain cup, to which basil oil is added drop by drop, mix well until the oil emulsifies.

Pregătirea substanţelor medicamentoase. Se cântaresc la balanţa analitică cantităţile necesare de substanţe medicamentoase. Preparation of medicinal substances. The necessary quantities of medicinal substances are weighed on the analytical balance.

Încorporarea substanţelor medicamentoase în emulsia primară. La emulsia primară se adaugă în porţiuni apă purificată (circa 1⁄2 din volumul ei) şi excipienţii. Loratadinul şi dexametazonul se dizolvă în polietilenglicol 400 şi se amestecă cu nipaginul în prealabil dizolvat într-o cantitate minimă de apă purificată din restul volumului; apoi se adaugă ciprofloxacina dizolvată în cantitatea minimă de apă din restul volumului. Se amestecă bine şi se omogenizează emulsia. Se măsoară pH-ul emulsiei şi dacă este cazul se ajustează cu ajutorul soluţiei tampon de citrat cu pH=7,8 (1 ml) până la pH-ul optimal 4,5…5,0. Emulsia obţinută este transferată într-un pahar gradat de 50 ml şi se completează până la cota necesară cu restul solventului. Emulsia obţinută are un aspect omogen, este lipsită de particule în suspensie, are un miros plăcut de ulei volatil de busuioc. Incorporation of medicinal substances into the primary emulsion. Purified water (about 1⁄2 of its volume) and excipients are added to the primary emulsion in portions. Loratadine and dexamethasone are dissolved in polyethylene glycol 400 and mixed with nipagin previously dissolved in a minimum amount of purified water from the rest of the volume; then ciprofloxacin dissolved in the minimum amount of water in the rest of the volume is added. Mix well and homogenize the emulsion. The pH of the emulsion is measured and, if necessary, adjusted with the citrate buffer solution with pH=7.8 (1 ml) until the optimal pH 4.5...5.0. The obtained emulsion is transferred into a 50 ml graduated glass and filled up to the required level with the rest of the solvent. The emulsion obtained has a homogeneous appearance, is free of suspended particles, and has a pleasant smell of volatile basil oil.

Amestecul se ambalează în recipiente din sticlă întunecată cu capacitatea de 50 g, se etanşează cu dop din masă plastică. The mixture is packed in dark glass containers with a capacity of 50 g, sealed with a plastic stopper.

Exemplu Example

Experimentele au fost efectuate pe 15 şoricei de laborator, masculi cu vârsta de 12 săptămâni şi greutatea corporală de 18…24 g la iniţierea studiului. Animalele de laborator au fost repartizate în 3 grupuri a câte 5 şoricei. La toate animalele până la iniţierea studiului s-a efectuat otoscopia pentru excluderea otitei. The experiments were performed on 15 laboratory mice, males aged 12 weeks and body weight of 18...24 g at the start of the study. The laboratory animals were divided into 3 groups of 5 mice each. Otoscopy was performed on all animals before the start of the study to rule out otitis.

Otita externă experimentală a fost provocată prin administrarea în conductul auditiv unilateral la fiecare animal de laborator a culturii Staphylococcus aureus 0,05 ml. Otita a fost diagnosticată prin otoscopie cu stabilirea următoarelor simptome: hiperemia tegumentelor urechii externe şi a conductului auditiv extern, culoarea roz a membranei timpanice, eliminări auriculare în conductul auditiv extern, înclinarea caracteristică a capului spre urechea afectată (în unele cazuri). Peste 3 zile după modelarea otitei acute a fost început tratamentul maladiei. Experimental otitis externa was induced by administering 0.05 ml of Staphylococcus aureus culture to each laboratory animal in the unilateral auditory canal. Otitis was diagnosed by otoscopy with the establishment of the following symptoms: hyperemia of the integuments of the external ear and the external auditory canal, pink color of the tympanic membrane, auricular discharges in the external auditory canal, the characteristic inclination of the head towards the affected ear (in some cases). More than 3 days after the modeling of acute otitis, the treatment of the disease was started.

La I grup s-a administrat preparatul studiat, la grupul II - separat concentraţii similare de ciprofloxacin, loratadin, dexametazon şi ulei de busuioc, la grupul 3 s-a administrat sol. Otinum. La toate grupele preparatele s-au administrat cu pipeta în urechea externă, câte 1 picătură de 2 ori pe zi. Zilnic s-a efectuat otoscopia pentru a stabili nivelul de afectare. La necesitate la animalele de laborator s-a efectuat toaleta conductului auditiv cu soluţie fiziologică. Vindecarea a fost determinată prin: lipsa eliminărilor în conductul auditiv extern, lipsa hiperemiei pielii din ureche, culoarea surie a membranei timpanice cu punctele de reper evidenţiate. La I grup vindecarea a fost constatată după 2…3 zile de administrare a preparatului studiat; la grupul II - după 4…5 zile de administrare; la grupul III - după 5…6 zile de administrare. Group I was administered the studied preparation, group II - separately similar concentrations of ciprofloxacin, loratadine, dexamethasone and basil oil, group 3 was administered salt. Otinum. In all groups, the preparations were administered with a pipette in the external ear, 1 drop twice a day. Daily otoscopy was performed to determine the level of damage. If necessary, laboratory animals were cleaned of the auditory canal with physiological solution. The healing was determined by: the lack of elimination in the external auditory canal, the lack of hyperemia of the skin in the ear, the tympanic membrane's brown color with highlighted landmarks. In the 1st group, healing was observed after 2...3 days of administration of the studied preparation; in group II - after 4...5 days of administration; in group III - after 5...6 days of administration.

În baza cercetării farmaceutice şi farmacologice a principiilor active ale ciprofloxacinei, loratadinului, dexametazonului şi uleiului de busuioc în combinaţie a fost elaborat un produs medicamentos nou cu acţiune polivalentă, manifestând următoarele proprietăţi: antiseptică, antiinflamatoare, regenerativă, antiexsudativă şi uşor anestezică, cu aplicare în clinică. Pentru prima oară se propune sub formă de picături auriculare combinaţia dintre un antibacterian fluorchinolon şi un remediu naturist în tratamentul afecţiunilor inflamatorii ale urechii. Based on the pharmaceutical and pharmacological research of the active principles of ciprofloxacin, loratadine, dexamethasone and basil oil in combination, a new medicinal product with polyvalent action was developed, showing the following properties: antiseptic, anti-inflammatory, regenerative, anti-exudative and slightly anesthetic, with application in clinic. For the first time, the combination of a fluoroquinolone antibacterial and a natural remedy in the treatment of inflammatory ear conditions is proposed in the form of ear drops.

Aşadar, a fost elaborat în laboratoarele catedrelor Universităţii un preparat medicamentos ce manifestă proprietăţi antiseptice, antiinflamatoare, regenerative. Therefore, a medicinal preparation with antiseptic, anti-inflammatory, regenerative properties was developed in the laboratories of the University departments.

1. Matcovschi C., Procopişin V., Parii B. Ghid farmacoterapeutic. Chişinău, 2006, p. 968 1. Matcovschi C., Procopisin V., Parii B. Pharmacotherapeutic guide. Chisinau, 2006, p. 968

Claims (1)

Preparat medicamentos pentru tratamentul otitelor, care conţine pentru 50 ml:Medicinal preparation for the treatment of otitis, which contains for 50 ml: ciprofloxacină clorhidrat, g 0,148…0,152 ulei volatil de busuioc, g 0,198…0,202 loratadin, g 0,009…0,015 dexametazon, g 0,009…0,015 polisorbat 20, g 1,990…2,010 polietilenglicol 400, g 4,990…5,010 nipagin, g 0,019…0,020 soluţie tampon de citrat cu pH 7,8, g 0,010…0,020 apă distilată restul. ciprofloxacin hydrochloride, g 0.148...0.152 volatile oil of basil, g 0.198...0.202 loratadine, g 0.009...0.015 dexamethasone, g 0.009...0.015 polysorbate 20, g 1.990...2.010 polyethylene glycol 400, g 4.990...5.010 nipagin, g 0.019 ...0.020 buffer solution of citrate with pH 7.8, g 0.010...0.020 distilled water the rest.
MDA20130100A 2013-12-27 2013-12-27 Medicinal preparation for the treatment of otitis MD4291C1 (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3369422A4 (en) * 2015-10-29 2018-12-05 Teika Pharmaceutical Co., Ltd. External preparation

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US4472405A (en) * 1982-11-12 1984-09-18 Riker Laboratories, Inc. Antimicrobial 6,7-dihydro-5,8-dimethyl-9 fluoro-1-oxo-1H, 5H-benzo (ij) quinolizine-2-carboxylic acid and derivatives
US4730000A (en) * 1984-04-09 1988-03-08 Abbott Laboratories Quinoline antibacterial compounds
US4704459A (en) * 1985-01-23 1987-11-03 Toyama Chemical Co., Ltd. Process for producing 1-substituted aryl-1,4-dihydro-4-oxonaphthyridine derivatives, and processes for producing the intermediates
US4861779A (en) * 1985-09-18 1989-08-29 Pfizer Inc. Anti-bacterial substituted bridged-diazabicycloalkyl quinolone carboxylic acids
SU1560199A1 (en) * 1988-01-18 1990-04-30 Московский научно-исследовательский институт уха, горла и носа Method of treating chronic inflammatory process of middle ear and sinisitis
SU1811833A1 (en) * 1989-06-09 1993-04-30 Vladimir I Ivanov Method for administration of medicines into ear
RU2040235C1 (en) * 1992-08-31 1995-07-25 Владимир Германович Поздеев Method for curing acute and chronic inflammation of middle ear
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EP0733357B1 (en) * 1995-03-22 2002-07-03 Dompé S.P.A. Pharmaceutical formulations in form of thixotropic gel
RU2103969C1 (en) * 1995-08-09 1998-02-10 Юрий Петрович Ульянов Method for treating eczematous otitis
RU2085164C1 (en) * 1995-10-25 1997-07-27 Санкт-Петербургский научно-исследовательский институт уха, горла, носа и речи Method for surgical treatment of otitis media chronica
BG102370U (en) * 1998-04-03 1999-10-29 Khristov, Nikolaj A. Composition make-up for making ear plugs
FR2790200B3 (en) * 1999-02-26 2001-06-01 Sanofi Sa STABLE FORMULATION CONTAINING FUMAGILLIN
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RU2201736C1 (en) * 2001-12-24 2003-04-10 Закрытое акционерное общество "Брынцалов-А" Ear drops
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